Apparatus for photo reduction of contaminants in blood and blood products with calibration means

ABSTRACT

An apparatus for irradiating blood or blood products, preferably with ultra violet or visible light, to reduce contaminants in the blood or blood products. A removable radiometer having light integrating chambers detects the light intensity, allowing the radiation characteristics of the apparatus to be calibrated. A control circuit uses the measurements to control the delivery of an effective dose of illumination to blood or blood products in a bag or container. One or more light integrating optical chambers in the radiometer allow a single light sensor to sense light across an entire field. Thermistors in the irradiating apparatus or the radiometer or both sense the temperature of photo sensors. The control circuit compensates for temperature-dependant variations in the output of the photo sensors.

This application describes an apparatus for irradiating blood or bloodproducts, preferably with ultra violet or visible light, to reducecontaminants in the blood or blood products. A removable radiometerhaving light integrating chambers detects the light intensity, allowingthe radiation characteristics of the apparatus to be calibrated. Acontrol circuit uses the measurements to control the delivery of aneffective dose of illumination to blood or blood products in a bag orcontainer. One or more light integrating chambers in the radiometerallow a single light sensor to sense light across an entire field.

BACKGROUND

Contamination of whole blood or blood products with infectiousmicroorganisms such as HIV, hepatitis and other viruses and bacteriapresent a serious health hazard for those who must receive transfusionsof whole blood or administration of various blood products or bloodcomponents such as platelets, red cells, blood plasma, Factor VIII,plasminogen, fibronectin, anti-thrombin III, cryoprecipitate, humanplasma protein fraction, albumin, immune serum globulin, prothrombincomplex plasma growth hormones, and other components isolated fromblood. Blood screening procedures may miss pathogenic contaminants, andsterilization procedures which do not damage cellular blood componentsbut effectively inactivate all infectious viruses and othermicroorganisms have not heretofore been available.

In some circumstances, certain blood components may themselves beharmful to the desired blood product. For example, white blood cells,which are part of the donor's immune system, may cause an adversereaction in the recipient of a red blood cell product. Many white cellsare separated by centrifugation from the desired red blood cells, butsome usually remain mixed with the red blood cells. The undesired whiteblood cells may be considered a “contaminant” or “pathogen” with respectto the desired relatively pure red blood cell product. The white bloodcells may be inactivated in the same manner as an infectious virus ormicroorganism.

The use of pathogen inactivating agents include certainphotosensitizers, or compounds which absorb light of defined wavelengthsand transfer the absorbed energy to an energy acceptor, have beenproposed for inactivation of microorganisms found in blood products orfluids containing blood products. Such photosensitizers may be added tothe fluid containing blood or blood products and irradiated.

The photosensitizers which may be used in this invention include anyphotosensitizers known to the art to be useful for inactivatingmicroorganisms. A “photosensitizer” is defined as any compound whichabsorbs radiation at one or more defined wavelengths and subsequentlyutilizes the absorbed energy to carry out a chemical process. Examplesof photosensitizers which may be used for the reduction of pathogens inblood or blood products include porphyrins, psoralens, dyes such asneutral red, methylene blue, acridine, toluidines, flavine (acriflavinehydrochloride) and phenothiazine derivatives, coumarins, quinolones,quinones, and anthroquinones.

A number of systems and methods for irradiating pathogens in a fluidwith light either with or without the addition of a photosensitizer areknown in the art. For example, U.S. Pat. No. 5,762,867 is directedtoward a system for activating a photoactive agent present in a bodyfluid with light emitting diodes (LEDs).

U.S. Pat. No. 5,527,704 is directed toward an apparatus containing LEDsused to activate a fluid containing methylene blue.

U.S. Pat. No. 5,868,695 discloses using LEDs having a red color andemitting light at a wavelength of 690 nm in combination withbenzoporphrin derivative photosensitizers to inactivate red blood cells.As taught in this patent, at a wavelength of 690 nm, red blood cells areessentially transparent to radiation, and as such, the benzoporphorinderivatives absorb radiation at this wavelength to become activated.Also disclosed in this patent is the use of LEDs having a blue color andemitting light at a peak wavelength of 425 nm to inactivate platelets.

U.S. Pat. No. 5,658,722 discloses irradiating platelets using UVA1 lighthaving an emission peak near 365 nm. This patent teaches that damage toplatelets is caused by short UVA<345 nm, and unlike the presentinvention, calls for removing UVA wavelengths below 345 nm.

Use of light which is variably pulsed at a wavelength of 308 nm withoutthe addition of a photosensitizer to inactivate virus in a washedplatelet product is taught in an article by Prodouz et al. (Use ofLaser-UV for Inactivation of Virus in Blood Products; Kristina Prodouz,Joseph Fratantoni, Elizabeth Boone and Robert Bonner; Blood, Vol 70, No.2). This article does not teach or suggest the addition of aphotosensitizer in combination with light to kill viruses.

U.S. Pat. No. 6,843,961 is directed toward the reduction of pathogenswhich may be present in blood or blood products using light having peakwavelengths in combination with an endogenous photosensitizer.

Whether or not a photosensitizer is used, it is important that thedosage of radiation delivered to the blood or blood component beaccurately controlled. Proper calibration of the irradiation apparatusis, therefore, necessary.

SUMMARY OF THE INVENTION

The present invention provides an apparatus for irradiating a fluidcontaining blood products and pathogens, including a radiometer foraccurate calibration of delivered radiation. The apparatus comprisestreatment chamber having at least one radiation emitting source emittingradiation; a support platform for holding the fluid containing bloodcells or blood components to be irradiated; a control unit forcontrolling the radiation emitting source; and a removable radiometer inelectrical communication with the control unit, the radiometercomprising a first optical chamber having a aperture for receiving atleast some of the radiation and a photo sensor responsive to thereceived radiation in the optical chamber. The optical chamber maycomprise an elongated cavity or cylinder, with an aperture shaped as aslot extending parallel to a long dimension of the optical chamber. Thisaperture might be covered by or filled with a light transmittingmaterial such as quartz glass. An inner surface of the optical chambermay be “optically rough”, producing a diffuse or lambertion reflection.The inner surface may be coated with or made from TEFLON™ or othersuitable material.

The photo sensor may be coupled to a thermistor through a heat sink. Theoutput of the photo sensor may be correlated to a detected temperature,whereby a more accurate measurement of illumination may be obtained.

In a further aspect of the invention related to an illuminator, a photosensor in the illuminator responds to radiation emitted by the radiationsource and communicates a signal to the control unit. A thermistordetects temperature changes and communicates a signal to the controlunit, which correlates the photo sensor signal with respect to thetemperature signal. It has been found that the photo sensor signal is afunction both of received light and of temperature, and that actualillumination can be more accurately controlled if the illuminator sensesthe temperature of the photodiode. Further, the illuminator may comprisea plurality of light sources and a plurality of photo diodes, at leastsome of the photodiodes being mounted in a heat sink. The thermistor maybe coupled to the heat sink.

In another aspect of the invention the radiometer may further comprise afirst integrating chamber coupled to the first optical chamber by anopening, which may be a second slot. The second slot may be generallyperpendicular to the first slot with respect to an axis of symmetry ofthe first optical chamber. Where there are two or more coupled opticalchambers, the sensor is preferably in the last chamber, for example, inthe first integrating chamber.

In a further aspect of the invention, the sensor is recessed away froman inner surface of the optical chamber. This may eliminate the use of abaffle. The recess may be “apodized”, that is, optically sharp cornersor discontinuities may be removed. The sensor may be mounteddiametrically across the first optical chamber from the second slot.

The apparatus may also have a second radiation emitting source emittingradiation, wherein the radiometer is mounted between the first radiationemitting source and the second radiation emitting source. The radiometermay further comprise a second optical chamber having a third aperturefor receiving at least some of said radiation from the second radiationsource and a second photo sensor responsive to the radiation received inthe third optical chamber.

In another embodiment of the invention, the apparatus comprises a firstintegrating chamber coupled to the first optical chamber by an openingand a second integrating chamber coupled to the second optical chamberby another opening. The optical chambers may be parallel, elongatedcylinders having substantially parallel longitudinal axes of symmetryand the apertures and the openings may be slots, the slots beingsubstantially parallel to the axes of symmetry.

These and other features of the invention will be apparent from thefollowing detailed description, taken with reference to the accompanyingdrawings.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a cross-sectional view of a treatment chamber in anilluminator which may be used in the present invention.

FIG. 2 is a cross-sectional view of another treatment chamber.

FIG. 3 is a perspective view of an irradiation apparatus or illuminatorcontaining a treatment chamber.

FIG. 4 is a top plan view of elements of a treatment chamber, with acalibration radiometer.

FIG. 5 is a cross-sectional plan view of the elements of FIG. 4, takenalong line 5-5 of FIG. 4.

FIG. 6 is a cross-sectional plan view of the elements of FIG. 4, takenalong line 6-6 of FIG. 4.

FIG. 7 is a perspective view of a radiometer.

FIG. 8 is a further perspective view of the radiometer of FIG. 7.

FIG. 9 is an exploded perspective view of a four-chamber radiometer.

FIG. 10 is a schematic diagram of an amplifier for use in theradiometer.

DETAILED DESCRIPTION

The term “blood product” as used herein includes all blood constituentsor blood components and therapeutic protein compositions containingproteins derived from blood as described above. Fluids containingbiologically active proteins other than those derived from blood mayalso be treated by the methods and devices of this invention.

Photosensitizers may include compounds which preferentially adsorb tonucleic acids, thus focusing their photodynamic effect uponmicroorganisms and viruses with little or no effect upon accompanyingcells or proteins. Other types of photosensitizers are also useful inthis invention, such as those using singlet oxygen-dependent mechanisms.

Most preferred are endogenous photosensitizers. The term “endogenous”means naturally found in a human or mammalian body, either as a resultof synthesis by the body or by ingestion as an essential foodstuff (e.g.vitamins) or formation of metabolites and/or byproducts in vivo.Examples of such endogenous photosensitizers are alloxazines such as7,8-dimethyl-10-ribityl isoalloxazine (riboflavin),7,8,10-trimethylisoalloxazine (lumiflavin), 7,8-dimethylalloxazine(lumichrome), isoalloxazine-adenine dinucleotide (flavin adeninedinucleotide [FAD]), alloxazine mononucleotide (also known as flavinmononucleotide [FMN] and riboflavin-5-phosphate), vitamin Ks, vitamin L,their metabolites and precursors, and napththoquinones, naphthalenes,naphthols and their derivatives having planar molecular conformations.The term “alloxazine” includes isoalloxazines. Endogenously-basedderivative photosensitizers include synthetically derived analogs andhomologs of endogenous photosensitizers which may have or lack lower(1-5) alkyl or halogen substituents of the photosensitizers from whichthey are derived, and which preserve the function and substantialnon-toxicity thereof. When endogenous photosensitizers are used,particularly when such photosensitizers are not inherently toxic or donot yield toxic photoproducts after photo radiation, no removal orpurification step is required after decontamination, and a treatedproduct can be directly returned to a patient's body or administered toa patient in need of its therapeutic effect without any further requiredprocessing. Using endogenous photosensitizers to inactivate pathogens ina blood product are described in U.S. Pat. No. 6,843,961, U.S. Pat. No.6,258,577 and No. 6,277,337, herein incorporated by reference in theirentirety to the amount not inconsistent. In U.S. Pat. No. 6,843,961, thephotosensitizer used in the examples is 7,8-dimethyl-10-ribitylisoalloxazine (riboflavin). Non-endogenous photosensitizers based onendogenous structures, such as those described in U.S. Pat. No.6,268,120, may also be used in the present invention, and isincorporated by reference herein. Upon exposure of the photosensitizerto light of a particular wavelength, the photosensitizer will absorb thelight energy, causing photolysis of the photosensitizer and any nucleicacid bound to the photosensitizer.

Microorganisms or pathogens which may be eradicated or inactivated usingpathogen inactivation agents or photosensitizers include, but are notlimited to, viruses (both extra-cellular and intracellular), bacteria,bacteriophages, fungi, blood-transmitted parasites, and protozoa.Exemplary viruses include acquired immunodeficiency (HIV) virus,hepatitis A, B and C viruses, sinbis virus, cytomegalovirus, vesicularstomatitis virus, herpes simplex viruses, e.g. types I and II, humanT-lymphotropic retroviruses, HTLV-III, lymphadenopathy virus LAV/IDAV,parvovirus, transfusion-transmitted (TT) virus, Epstein-Barr virus, andothers known to the art. Bacteriophages include Φ X174, Φ6, λ, R17, T₄,and T₂. Exemplary bacteria include but are not limited to P. aeruginosa,S. aureus, S. epidermis, L. monocytogenes, E. coli, K. pneumonia and S.marcescens.

The fluid to be pathogen inactivated has the photosensitizer addedthereto, and the resulting fluid mixture may be exposed to photoradiation of the appropriate peak wavelength and amount to activate thephotosensitizer, but less than that which would cause significantnon-specific damage to the biological components or substantiallyinterfere with biological activity of other proteins present in thefluid. Accurate control of the amount of radiation delivered to thefluid is, therefore, important.

The term peak wavelength as defined herein means that the light isemitted in a narrow range centered around a wavelength having aparticular peak intensity. Visible light for pathogen reduction may becentered around a wavelength of approximately 470 nm, and having amaximum intensity at approximately 470 nm. In another embodiment, thelight may be centered around a narrow range of UV light at anapproximate wavelength of 302 nm, and having a maximum intensity atapproximately 302 nm. The term light source or radiation source asdefined herein means an emitter of radiant energy, and may includeenergy in the visible and/or ultraviolet range, as further describedbelow.

The photosensitizer may be added directly to the fluid to be pathogeninactivated, or may be flowed into the photo-permeable containerseparately from the fluid being treated, or may be added to the fluidprior to placing the fluid in the photo-permeable treatment container.The photosensitizer may also be added to the photo-permeable containereither before or after sterilization of the treatment container.

The fluid containing the photosensitizer may also be flowed into andthrough a photo-permeable container for irradiation, using a flowthrough type system. Alternatively, the fluid to be treated may beplaced in a photo-permeable container which is agitated and exposed tophoto radiation for a time sufficient to substantially inactivate themicroorganisms, in a batch-wise type system.

The term “container” refers to a closed or open space, which may be madeof rigid or flexible material, e.g., may be a bag or box or trough. Thecontainer may be closed or open at the top and may have openings at bothends, e.g., may be a tube or tubing, to allow for flow-through of fluidtherein. A cuvette has been used to exemplify one embodiment of theinvention involving a flow-through system. Collection bags, such asthose used with the TRIMA® and/or SPECTRA™ apheresis systems ofCaridianBCT, Inc., (f/k/a Cobe Laboratories, Inc. and Gambro BCT, Inc,Lakewood, Colo., USA), have been used to exemplify another embodimentinvolving a batch-wise treatment of the fluid.

The term “photo-permeable” means the material of the treatment containeris adequately transparent to photo radiation of the proper wavelengthfor activating the photosensitizer. In a flow-through system, thecontainer has a depth (dimension measured in the direction of theradiation from the photo radiation source) sufficient to allow photoradiation to adequately penetrate the container to contactphotosensitizer molecules at all distances from the light source andensure inactivation of pathogens in the fluid to be decontaminated, anda length (dimension in the direction of fluid flow) sufficient to ensurea sufficient exposure time of the fluid to the photo radiation. Thematerials for making such containers, as well as the depths and lengthsof the containers may be easily determined by those skilled in the art,and together with the flow rate of fluid through the container, theintensity of the photo radiation and the absorptivities of the fluidcomponents, e.g., plasma, platelets, red blood cells, will determine theamount of time the fluid should be exposed to photo radiation. Thecontainer used may be any container known in the art for holding fluidto be irradiated, including, but not limited to blood bags, cuvettes andtubing. One example, not meant to be limiting which may be used as thecontainer, is an Extended Life Platelet (ELP) bag available fromCaridianBCT, Inc. Another example of a suitable container is the toSangewald bag (available from Sangewald Verpackungen GmbH & Co. KG).

After treatment, the blood or blood product may be stored for laterdelivery to a patient, concentrated, infused directly into a patient orotherwise processed for its ultimate use.

FIG. 1 shows, in a cross-sectional view, the inside of a radiation ortreatment chamber of one type of apparatus that may be used in thepresent invention. The treatment chamber shown in FIG. 1 may be used inbatch-wise systems, however, it should be noted that similar elementsmay also be used in flow-through systems. It should be noted thatthroughout the description of the invention, like elements have beengiven like numerals. The apparatus 10, used for inactivating a fluidwhich may contain pathogens, consists of an radiation chamber 12 havingat least one source of radiation 14. In one preferred embodiment (FIG.1), the radiation chamber may contain a second source of radiation 16. Asingle light source, as shown in FIG. 2, may also be used. Eachradiation source 14 and 16 respectively, is depicted as including aplurality of discrete radiation-emitting elements 18, 30. The radiationchamber 12 further consists of a support platform 20 for supporting afluid container 22 containing the fluid to be irradiated, and a controlunit 24.

As introduced above, two sources of radiation are shown within radiationchamber 12. Radiation source 14 may be located along the top portion ofthe radiation chamber 12 above the container 22, which holds or containsthe fluid to be irradiated, while radiation source 16 may be locatedalong the bottom portion of the radiation chamber 12 below the container22. Although not shown, radiation sources may also be located along someor all of the sides of the radiation chamber 12 perpendicular to thecontainer 22. The radiation chamber 12 may alternatively contain asingle radiation source at any location within the radiation chamber 12and still comply with the spirit and scope of the present invention.

The upper radiation source 14 includes an upper support substrate 36supporting a plurality of discrete radiation emitting elements ordiscrete light sources (see discrete source 18 as one example) mountedthereon. As further depicted in FIG. 1, the lower radiation source 16includes a lower support substrate 28 which also supports a plurality ofdiscrete radiation emitting elements or discrete light sources (seediscrete source 30 as another example). Lower support substrate 28preferably runs parallel to support platform 20. The support substrates36, 28 may be substantially flat as shown, or may be in an arcuateshape, or may be in a shape other than arcuate, without departing fromthe spirit and scope of the invention.

The support substrate may or may not have reflective surfaces. In afurther alternative configuration, the reflective surface may notcontain any light sources. Such a reflective surface containing no lightsources (not shown) may be located within the radiation chamber 12 on aside opposite from the radiation source. The support platform 20 mayhave a reflective surface 32. This reflective surface 32 on supportplatform 20 may be in place of, or may be in addition to anotherreflective surface within the radiation chamber. There may also be noreflective surfaces at all within the radiation chamber.

In any of these reflective surface embodiments, the reflective surfacemay be coated with a highly reflective material which serves to reflectthe radiation emitted from the lights back and forth throughout thetreatment chamber until the radiation is preferably completely absorbedby the fluid being irradiated. The highly reflective nature of thereflective surface reflects the emitted light back at the fluid-filledbag or container 22 with minimum reduction in the light intensity.

In FIG. 1, support platform 20 is positioned within the radiationchamber 12. The support platform 20 may be located substantially in thecenter of the radiation chamber (as shown in FIG. 1), or may be locatedcloser to either the top portion or the bottom portion of the treatmentchamber. The support platform 20 supports the container 22 containingthe fluid to be irradiated. Additionally or alternatively, the platform20 may be made of a photo-permeable material to enable radiation emittedby the lights to be transmitted through the platform and penetrate thefluid contained within the container 22. The platform may also be a wireor other similar mesh-like material to allow maximum lighttransmissivity therethrough.

The support platform 20 is preferably capable of movement in multipledirections within the radiation chamber 12. One type of agitation systemused might be similar to the Helmer flatbed agitation system availablefrom Helmer Corp. (Noblesville, Ind., USA). This type of agitatorprovides to and fro motion. Other types of agitators may also be used toprovide a range of motion to the fluid contained within the container22. For example, the support platform might be oriented in a verticaldirection with the light substrates 36 and 28 also oriented in avertical direction. The support platform 20 may alternatively rotate inmultiple possible directions within the radiation chamber in varyingdegrees from between 0° to 360°. Support platform 20 may also oscillateback and forth, or side to side along the same plane. As a furtheralternative, one or more of the light sources may also move in acoordinated manner with the movement of the support platform. Suchoscillation or rotation would enable the majority of the photosensitizerand fluid contained within the container 22 to be exposed to the lightemitted from each of the discrete radiation sources (e.g. discretesources 18 and 30), by continually replacing the exposed fluid at thelight-fluid interface with fluid from other parts of the bag not yetexposed to the light. Such mixing continually brings to the surface newfluid to be exposed to light. The movement of both the support platform20 and/or the radiation sources 14 and 16 may be controlled by controlunit 24. The control unit 24 may also control the rate of lightemission.

In a preferred embodiment each discrete light source 18 and 30 emits apeak wavelength of light to irradiate the fluid contained in bag 22. Thepeak wavelength of light emitted by each discrete light source isselected to provide irradiation of a sufficient intensity to activateboth the photosensitizer in a pathogen inactivation process as well asto provide sufficient penetration of light into the particular fluidbeing irradiated, without causing significant damage to the blood orblood components being irradiated. The preferred photosensitizer isriboflavin. To irradiate a fluid containing red blood cells andriboflavin, it is preferred that each discrete light source 18 and 30 beselected to emit light at a peak wavelength of about 302 nm.Alternatively, 470 nm light might be used. The 470 nm of light is closeto the optimal wavelength of light to both photolyse riboflavin, andalso to enable significant penetration of the fluid containing red bloodcells by the light.

If desired, the light sources 18 and 30 may be light emitting diodes andmight be pulsed. Pulsing the light may be advantageous because theintensity of light produced by the light sources may be increaseddramatically if the lights are allowed to be turned off and restedbetween light pulses. Pulsing the light at a high intensity also allowsfor greater depth of light penetration into the fluid being irradiated,thus allowing a thicker layer of fluid to be irradiated with each lightpulse.

The light sources 18 as shown in FIG. 3 may be fluorescent orincandescent tubes, which stretch the length of the irradiation chamber,or may be a single light source which extends the length and width ofthe entire chamber (not shown). LEDs may also be used in thisembodiment. As shown in FIG. 3, the support platform 20 may be locatedwithin and/or forming part of a drawer 34. The support platform 20 maycontain gaps 36 or holes or spaces within the platform 20 to allowradiation to penetrate through the gaps directly into the container 22containing fluid to be irradiated.

A cooling system may also optionally be included. Air cooling using atleast one fan 38 may be preferred but it is understood that otherwell-known systems can also be used. Although not shown in FIG. 3, themethod may also include the use of temperature sensors and other coolingmechanisms where necessary to keep the temperature below temperatures atwhich desired proteins and blood components in the fluid beingirradiated are damaged. Preferably, the temperature is kept betweenabout 0° C. and about 45° C., more preferably between about 4° C. andabout 37° C., and most preferably about 28° C.

The present invention includes a removable radiometer 40 that has thegeneral shape of a blood bag 22. When placed on the support platform 20and electrically connected to the controller 24, the radiometer 40detects the intensity of incident light, preferably ultraviolet light,thereby allowing for calibration of the apparatus 10. Once calibrated,the controller 24 will be able to adjust exposure time and lightintensity to deliver a desired dose of radiation to a blood bag and itscontents. As shown in FIGS. 4, 5 and 6, the support platform or platen20 carries the radiometer 40 backwards and forwards parallel to theultraviolet florescent light sources 18. The stroke distance allows thesensing apparatus (described below) of the radiometer to “view” thelight sources 18, 30. Each of the light sources 18, 30 has an associatedphoto sensor 42, 44 (FIG. 6) in electrical communication with thecontroller 24. During calibration, the controller 24 correlates thesignals from the photo sensors 42, 44 to the output of the radiometer40. When the radiometer 40 has been removed and replaced with a bloodbag, the controller 24 will control the dose of radiation received bythe blood bag based on the calibrated signals received from the photosensors 42, 44.

The photo sensors 42, 44 may be mounted in heat sinks 110, 112.Thermistors 114, 116 detect the temperature of the photo sensors 42, 44as represented by the temperature of the heat sinks 110, 112 andcommunicate a signal to the controller 24. It has been found that theoutput signals of the photo sensors 42, 44 are dependant not only on theincident light received by a photo sensor, but also on temperature, thatis, increased temperature will elevate the output of the photo sensorfor the same intensity of incident light. With signals from both thethermistor and the photo sensor, the controller can more accuratelycontrol the dose of radiation received by the blood bag and itscontents.

The radiometer 40 comprises at least one elongated, cylindrical opticalchamber. If light is supplied solely from one side, for example, fromthe upper lamps 18, a first or upward-opening optical chamber 46 may beprovided, oriented generally perpendicularly to the tubes 18 and to areciprocating movement of the platen 20. An upper surface 48 of theradiometer 40 has a slot 50 parallel to the elongated axis of theoptical chamber 46, which allows light from the lamps 18 to enter theoptical chamber. The edges 52 of the slot 50 are preferably chamfered toallow light from most of the length of the lamps to be received in thechamber 46. Reciprocating movement of the platen 20 brings additionallengths of the lamps at each end into the view of the chamber 46. Thus,the radiation received through the slot 50 approximates the radiationreceived by a blood sample and sample bag along a line at the positionof the slot. Because the chamber “averages” the non-uniform light fieldemitted by the lamps 18, the exposure on this line can be used tocalculate the total exposure dose received by the sample.

An inner surface 54 of the optical chamber 46 is optically rough andcoated with or made from a suitable substance such as TEFLON™ material,allowing light received in the chamber to reflect within the chamber insuch a way that the light field becomes averaged at any point within thechamber. A single photo sensor 56, mounted in the inner surface 54perpendicularly from the slot 50, can sense an intensity representativeof the radiation being received along the entire length of the slot.Preferably, the photo sensor 50 is recessed away from the inner surface54, to reduce the likelihood of a beam of light or radiation from thelamps 18 falling directly on the photo sensor 56 without at least onereflection from the inner surface 54 of the chamber. Multiple photosensors may also be used.

In an embodiment having a lower bank of lamps 30, the radiometer 40preferably has a second downward-opening optical chamber 58. The secondoptical chamber 58 is oriented parallel to the first optical chamber 46and also comprises a slot 60 in a lower surface 62 of the radiometer 40,the slot 60 being parallel to the elongated axis of the second opticalchamber 58, but oriented in an opposite direction from the slot 50 inthe first chamber 46, which allows light from the lower lamps 30 toenter the second optical chamber 58. The edges 64 of the slot 60 arepreferably chamfered, as explained above, and reciprocating movement ofthe platen 20 brings additional lengths of the lower lamps at each endinto the view of the lower chamber 58. An inner surface 66 of theoptical chamber 58 is optically rough and coated with or made from asuitable substance such as TEFLON™ material. As explained above, asingle photo sensor 68, mounted in the inner surface 66 perpendicularlyfrom the slot 60, is recessed away from the inner surface 66. Although asingle photo sensor in each optical chamber is preferred, a plurality ofphoto sensors could also be used.

The radiometer 40 comprises an upper shell 71 and a lower shell 70. Thelower shell 70, as shown in FIG. 7 and FIG. 8, has a bottom surface 72and a peripheral wall 74, the peripheral wall having the general shapeof a blood bag of a type that might be used in the illuminator 10. Theupper shell 71 has a top surface 48 and a mating peripheral wall 78 (seeFIG. 5 and FIG. 6), adapted to fit against the peripheral wall 74 of thelower shell 70. As explained above, first and second optical chambers46, 58 are provided. These chambers 46, 58 comprise matinghalf-cylinders 80, 82 in the lower shell 70 and upper half-cylinders inthe upper shell 71. In the embodiment shown in FIG. 7 and FIG. 8, thechambers 46, 58 are within an inner box 118 having a lower portion 120and an upper portion 122. Heat sinks 132, 134 cover the photo diodes 56,68 on the outside of the box 118. Thermistors 136, 138, in thermalcontact with the heat sinks 132, 134 respond to the temperature of theheat sinks, which is also representative of the temperature of the photodiodes 56, 68. The output of the photodiodes is a function not only ofthe incident illumination, but also of the temperature of thephotodiode. Thus, as the temperature of the photodiode increases, theoutput current of the photodiode will also rise, even if theilluminating radiation is constant. In order to provide an accuratemeasure of the illumination (as well as an accurate dose of radiation bythe illuminator), the control circuit 24 compensates both for thetemperature of the photodiodes in the radiometer during calibration andfor the temperature of the photodiodes in the illuminator during viralinactivation. Electrical connecting wires (not shown) may pass throughgaps 124, 126 between the shells 70, 71 and the box 118, providingelectrical connections between the photo diodes 56, 68, amplifiercircuits 128, 130, thermistors 136, 138 and the control unit 24. Thewires pass as a cable through a block 140 (FIG. 5), comprised of twomating halves 142, 144, the lower half 142 of which is shown in FIG. 7and FIG. 8. Spring plates 146, 148 may be provided adjacent the block onboth the lower shell 70 and the upper shell 71, which may be engaged bya clamp (not shown) that holds a blood bag in position on theilluminator.

Each of the photo sensors 56, 68 is electrically coupled totransimpedance amplifiers 128, 130 respectively. The amplifiers 128, 130are further electrically connected through a communications cable to thecontrol unit 24. Male and female plugs (not shown) may be provided sothat the radiometer may be selectively coupled to the control unit 24for calibrating the apparatus, and then removed for ordinary operation.As shown in FIG. 11, the transimpedance amplifiers comprise anoperational amplifier 100 receiving input from a photo sensor 102. Thegain is controlled by both a manual variable resister 104 and a digitalvariable resister 106. The signal is then fed to a second operationalamplifier 108 before being conducted to the control unit 24. It isanticipated that the variable resisters will be initially adjusted incomparison to a standardized light source, and would not need furtheradjustment when used in connection with a pathogen inactivationapparatus.

To calibrate a pathogen in activation apparatus, the radiometer 40 issubstituted for a blood bag, and occupies the same location in theapparatus and has the same general shape as a blood bag containing bloodor blood components. The radiometer would be electrically connected tothe control unit 24 and exposed to radiation from the lamps 18, 30 for aselected period of time. Preferably, the platen 20 would also beagitated it the same manner as when a blood sample would be treated inthe apparatus. The output of the radiometer provides a benchmark to thecontrol unit 24 of exposure intensity per unit time, from which adesired dose of radiation can be calculated. After calibration of theapparatus, units of blood or blood components in appropriate translucentor transparent bags can be placed in the pathogen inactivation apparatusand exposed to controlled quantities of radiation.

Another embodiment of the radiometer 40 is shown in FIG. 9. In thisembodiment, the first optical chamber 46 is connected to a firstelongated, cylindrical integrating chamber 84 through a third slot 86.The walls of the first integrating chamber 84 are also optically roughand preferably made from TEFLON™ material or TEFLON-coated. In thisembodiment, the photo sensor 56 is mounted in the inner wall 90 of thefirst integrating chamber, rather than in the inner wall of the firstoptical chamber.

Similarly, a second elongated, cylindrical integrating chamber 92connects to the second optical chamber 58 through a fourth slot 94. Asabove, the photo sensor 68 is mounted in the inner wall 96 of the secondintegrating chamber 92, rather than in the inner surface 66 of thesecond optical chamber 58. The inner wall 96 is also optically rough andpreferably made from TEFLON™ material or TEFLON-coated. The additionalfirst and second integrating chambers 84, 92 further integrate thereceived illumination, providing a more representative measurement atthe respective photo sensors, but at the cost of a decrease in absoluteintensity.

It will be apparent to those skilled in the art that variousmodifications and variations can be made to the structure andmethodology of the present invention without departing from the scope orspirit of the invention. Rather, the invention is intended to covermodifications and variations provided they come within the scope of thefollowing claims and their equivalents.

1. A radiometer comprising a first optical chamber consisting of anelongated cavity symmetrical about an axis through a long dimension ofsaid chamber and having a first slot for receiving at least someradiation from outside said optical chamber, said slot being parallel tosaid axis, and a photo sensor responsive to said received radiationmounted in said optical chamber perpendicularly from said slot withrespect to said axis; a second optical chamber consisting of anelongated cavity symmetrical about a second axis through a longdimension of said second chamber and having a third slot for receivingat least some radiation from outside said second chamber, said slotbeing parallel to said second axis, and a second photo sensor responsiveto said received radiation mounted in said second optical chamberperpendicularly from said third slot with respect to said second axis; afirst integrating chamber coupled to said first optical chamber by afirst opening; and a second integrating chamber coupled to said secondoptical chamber by a second opening, said openings being slots, saidslots being substantially parallel to said axes of their respectiveoptical chambers.
 2. The radiometer of claim 1 wherein said opticalchamber comprises a cylinder.
 3. The radiometer of claim 2 wherein aninner surface of said optical chamber is optically rough.
 4. Theradiometer of claim 3 wherein said inner surface is Teflon.
 5. Theradiometer of claim 1 further comprising a first integrating chambercoupled to said first optical chamber by an opening.
 6. The radiometerof claim 5 wherein said first integrating chamber is elongated andwherein said opening is a second slot.
 7. The radiometer of claim 6wherein said second slot is generally perpendicular to said first slotwith respect to said axis of said first optical chamber.
 8. Theradiometer of claim 7 wherein said sensor is in said first integratingchamber.
 9. The radiometer of claim 8 wherein said sensor is recessedaway from an inner surface of said first integrating chamber.
 10. Theradiometer of claim 8 wherein said sensor is mounted diametricallyacross said first integrating chamber from said second slot.
 11. Theradiometer of claim 1 wherein said optical chambers comprise parallelcylinders.
 12. The radiometer of claim 11 wherein said photo sensors arerecessed away from an inner wall of their respective optical chamber.13. The radiometer of claim 1 wherein said slots in said first andsecond optical chambers are substantially perpendicular to said slotsbetween said first and second optical chambers and said first and secondintegrating chambers respectively with respect to said axes of saidfirst and second optical chambers respectively.
 14. The radiometer ofclaim 13 wherein said first sensor is in said first integrating chamberand said second sensor is in said second integrating chamber.
 15. Theradiometer of claim 14 wherein said first sensor is recessed away froman inner surface of said first integrating chamber and said secondsensor is recessed away from an inner surface of said second integratingchamber.
 16. The radiometer of claim 15 wherein said first sensor ismounted diametrically across said first integrating chamber from saidslot in said first integrating chamber and said second sensor is mounteddiametrically across said second integrating chamber from said slot insaid second integrating chamber.
 17. The radiometer of claim 1 whereinsaid radiometer further comprises a thermistor in thermal communicationwith said photo sensor and in electrical communication with said controlunit, wherein said control unit is adapted to compensate for variationsin the output of said photo sensor in response to an output of saidthermistor.
 18. The radiometer of claim 17, wherein a heat sink connectssaid photo sensor to said thermistor.